Retroviruses commonly undergo genetic alterations. These include point mutations, which have been documented with the lenti viruses such as visna, EIAV and the AIDS virus, as well as major substitutions with host genes which have been documented with murine leukemia viruses (MuLVs). Ecotropic MuLVs (MuLVs which infect only murine cells) undergo recombination with endogenous sequences of the mouse to generate polytropic viruses (MuLVs which infect cells of other species). The major goal of this project is to characterize recombinant MuLVs generated between ecotropic MuLVs and gene sequences of the mouse, and to define their role in the disease process. Initial studies demonstrated that polytropic MuLVs isolated after inoculation of an erythroleukemia virus, Friend (F) MuLV, were derived from different endogenous sequences than those isolated after inoculation of a lymphocytic leukemia virus, Moloney (M) MuLV. This finding has been confirmed using an immunofluorescence assay to analyze the frequency of recombinant MuLV types present in large virus populations from infected mice. Further studies have indicated that pseudotyping of the ecotropic virus by envelope proteins of polytropic viruses correlated with the development of lymphocytic leukemia. Pseudotyping yeilds ecotropic virions with an altered range of infectivity and may facilitate the infection of cells which ultimately become transformed. Ecotropic pseudotyping may rreflect the generation of specific types of polytropic viruses. AKR mice harbor an endogenous ecotropic virus which recombines with endogenous nonecotropic sequences to generate oncogenic polytropic viruses. These recombinant viruses possess two nonecotropic sequences; one corresponding to the 5' end of the envelope gene (env), and another which includes the long terminal repeat (LTR). The nonecotropic sequences are thought to be derived from two different retroviral species. Intermediates have been described which contain the LTR sequence, however the source of the 5' env sequence was not known. We have identified an intermediate containing the 5' env sequence in young AKR mice.